Corbus Pharmaceuticals’ phase 1b obesity trial has generated evidence that its CB1 inverse agonist may be less prone to the neuropsychiatric side effects that haunted Novo Nordisk and Sanofi.
Sanofi won European approval for a CB1 receptor blocker weight loss drug, Acomplia, in 2006, only for evidence that the medicine doubles the risk of psychiatric disorders to force the product off the market three years later. Novo resurrected interest in the mechanism in 2023 by inking a deal to buy Inversago Pharma for up to $1.1 billion. But the following year the Danish drugmaker reported neuropsychiatric side effects from Inversago's drug monlunabant in a phase 2 trial.
With Novo axing monlunabant, Corbus has a chance to establish CRB-913 as the frontrunner in the CB1 race. The phase 1b data contain positive signs mixed with scope to question whether Corbus has seized the opportunity, leaving the biotech’s stock up 4% at $8.48 in early trading.
At a Jefferies event in June, Corbus CEO Yuval Cohen, Ph.D., said “pretty much the only question is are we going to look safer than monlunabant in terms of the neuropsych [adverse events].” The study succeeded by Cohen’s yardstick, with Corbus reporting lower rates of depression, anxiety, irritability and insomnia than Novo saw in its phase 2a trial.
Rates of the adverse events on the highest dose of CRB-913 ranged from 0% to 9.7%. Corbus compared its data to placebo and GLP-1 receptor agonists, showing that small numbers of people report psychiatric events while taking drugs such as Novo’s Wegovy and Eli Lilly’s Zepbound.
Corbus reported placebo-adjusted weight loss of up to 5% at Week 12, in line with the 5.8% that Novo saw at Week 16 of its phase 2a trial and well ahead of the efficacy of Acomplia. The CRB-913 result is in the same ballpark as the phase 3 data that Novo published on oral Wegovy. There was no evidence that weight loss was plateauing at Week 12, pointing to the potential for deeper declines in longer trials.
Little evidence suggests that CRB-913 can improve significantly on the efficacy of oral Wegovy, but Corbus’ candidate could be a more tolerable option. CRB-913’s rates of vomiting, nausea and constipation compare favorably to data for Wegovy pill and Lilly’s Foundayo, although numerically more people had diarrhea on CRB-913 than on the existing oral obesity drugs.